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      Real-world evidence of cytomegalovirus reactivation in non-Hodgkin lymphomas treated with bendamustine-containing regimens

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          Abstract

          Cytomegalovirus (CMV) reactivation during chemotherapy or after organ or hematopoietic stem cell transplantation is a major cause of morbidity and mortality, and the risk of reactivation increases with patients’ age. Bendamustine, an alkylating agent currently used for treatment of indolent and aggressive non-Hodgkin lymphomas, can augment the risk of secondary infections including CMV reactivation. In this real-world study, we described an increased incidence of CMV reactivation in older adults (age >60 years old) with newly diagnosed and relapsed/refractory indolent and aggressive diseases treated with bendamustine-containing regimens. In particular, patients who received bendamustine plus rituximab and dexamethasone were at higher risk of CMV reactivation, especially when administered as first-line therapy and after the third course of bendamustine. In addition, patients with CMV reactivation showed a significant depression of circulating CD4 + T cell count and anti-CMV IgG levels during active infection, suggesting an impairment of immune system functions which are not able to properly face viral reactivation. Therefore, a close and early monitoring of clinical and laboratory findings might improve clinical management and outcome of non-Hodgkin lymphoma patients by preventing the development of CMV disease in a subgroup of subjects treated with bendamustine more susceptible to viral reactivation.

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          The 2016 revision of the World Health Organization classification of lymphoid neoplasms.

          A revision of the nearly 8-year-old World Health Organization classification of the lymphoid neoplasms and the accompanying monograph is being published. It reflects a consensus among hematopathologists, geneticists, and clinicians regarding both updates to current entities as well as the addition of a limited number of new provisional entities. The revision clarifies the diagnosis and management of lesions at the very early stages of lymphomagenesis, refines the diagnostic criteria for some entities, details the expanding genetic/molecular landscape of numerous lymphoid neoplasms and their clinical correlates, and refers to investigations leading to more targeted therapeutic strategies. The major changes are reviewed with an emphasis on the most important advances in our understanding that impact our diagnostic approach, clinical expectations, and therapeutic strategies for the lymphoid neoplasms.
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            The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications.

            The World Health Organization classification of lymphoid neoplasms updated in 2008 represents a worldwide consensus on the diagnosis of these tumors and is based on the recognition of distinct diseases, using a multidisciplinary approach. The updated classification refined the definitions of well-recognized diseases, identified new entities and variants, and incorporated emerging concepts in the understanding of lymphoid neoplasms. However, some questions were unresolved, such as the extent to which specific genetic or molecular alterations define certain tumors, and the status of provisional entities, categories for which the World Health Organization working groups felt there was insufficient evidence to recognize as distinct diseases at this time. In addition, since its publication, new findings and ideas have been generated. This review summarizes the scientific rationale for the classification, emphasizing changes that have had an effect on practice guidelines. The authors address the criteria and significance of early or precursor lesions and the identification of certain lymphoid neoplasms largely associated with particular age groups, such as children and the elderly. The issue of borderline categories having overlapping features with large B-cell lymphomas, as well as several provisional entities, is reviewed. These new observations chart a course for future research in the field.
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              Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection.

              Cytomegalovirus establishes a lifelong latent infection following primary infection that can periodically reactivate with shedding of infectious virus. Primary infection, reactivation and reinfection during pregnancy can all lead to in utero transmission to the developing fetus. Congenital CMV infections are a major cause of permanent hearing loss and neurological impairment. In this literature review, we found that CMV infection was relatively common among women of reproductive age, with seroprevalence ranging from 45 to 100%. CMV seroprevalence tended to be highest in South America, Africa and Asia and lowest in Western Europe and United States. Within the United States, CMV seroprevalence showed substantial geographic variation as well, differing by as much as 30 percentage points between states, though differences might be explained by variation in the types of populations sampled. Worldwide, seroprevalence among non-whites tended to be 20-30 percentage points higher than that of whites (summary prevalence ratio (PR) = 1.59, 95% confidence interval (CI) = 1.57-1.61). Females generally had higher seroprevalences than males, although in most studies the differences were small (summary PR = 1.13, 95% CI = 1.11-1.14). Persons of lower socioeconomic status were more likely to be CMV seropositive (summary PR = 1.33, 95% CI = 1.32-1.35). Despite high seroprevalences in some populations, a substantial percentage of women of reproductive age are CMV seronegative and thus at risk of primary CMV infection during pregnancy. Future vaccine or educational campaigns to prevent primary infection in pregnant women may need to be tailored to suit the needs of different populations.
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                Author and article information

                Journal
                Open Med (Wars)
                Open Med (Wars)
                med
                Open Medicine
                De Gruyter
                2391-5463
                21 April 2021
                2021
                : 16
                : 1
                : 672-682
                Affiliations
                Hematology and Transplant Center, University Hospital “San Giovanni di Dio e Ruggi d’Aragona” , Salerno, 84131, Italy
                Clinical Pharmacology, University Hospital “San Giovanni di Dio e Ruggi d’Aragona” , Salerno, 84131, Italy
                Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno , Baronissi, 84081, Salerno, Italy
                Transfusion Medicine, Molecular Biology Section, University Hospital “San Giovanni di Dio e Ruggi d’Aragona” , Salerno, 84131, Italy
                Infectious Disease Unit, University Hospital “San Giovanni di Dio e Ruggi d’Aragona” , Salerno, 84131, Italy
                Department of Translational Medical Sciences, “Federico II” University , 80138, Naples, Italy
                Author notes
                [1]

                Equal contribution.

                tel: +39-089-673150, fax: +39-089-673153
                Article
                med-2021-0274
                10.1515/med-2021-0274
                8082049
                33981851
                bd697d82-8638-4ed5-b017-ef2705a5bb4f
                © 2021 Luca Pezzullo et al., published by De Gruyter

                This work is licensed under the Creative Commons Attribution 4.0 International License.

                History
                : 27 December 2020
                : 28 February 2021
                : 19 March 2021
                Page count
                Pages: 11
                Categories
                Research Article

                cytomegalovirus,non-hodgkin lymphoma,chemotherapy,immunity

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